| Suppression of Akt-HIF-1メ signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis |
| Sik-Won Choi1,#, Kwang-Sik Lee1,2,#, Jin Hwan Lee3, Hyeon Jung Kang1, Mi Ja Lee1, Hyun Young Kim1, Kie-In Park4, Sun-Lim Kim1, Hye Kyoung Shin5, Woo Duck Seo1,* |
1Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA),
2College of Crop Science and Biotechnology, Dankook University,
3Division of Research Development and Education, National Institute of Chemical Safety, Ministry of Environment,
4Division of Biological Sciences, College of Natural Science, Chonbuk National University,
5Department of surgery, Gangnam Severance Hospital, Yonsei University College of Medicine |
|
Abstract
The hypoxia-inducible factor (HIF)-1メ is a key regulator associated with tumorigenesis, angiogenesis, and metastasis. HIF-1メ regulation under hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. Here, we identify diacetyl atractylodiol (DAA) from Atractylodes japonica (A. japonica) as a potent HIF-1メ inhibitor that inhibits the Akt signaling pathway. DAA dose-dependently inhibited hypoxia-induced HIF-1メ and downregulated Akt signaling without affecting HIF-1メ protein stability. Furthermore, DAA prevented hypoxia-mediated angiogenesis as determined by in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays. DAA may be of use in the treatment of hypoxia-related tumorigenesis, including angiogenesis
|
| Abstract, Accepted Manuscript(in press) [Submitted on April 19, 2016, Accepted on July 18, 2016] |
|